Toxicity Assessment of the Crude Ethanolic Pod Extract of Swartzia madagascariensis Desv. in Rats

This study assessed toxicity of the crude ethanolic pod extracts of Swartzia madagascariensis Desv in Wistar rats. Forty (40) Wistar rats aged 8–10 weeks were orally administered with crude extracts from pods of S. madagascariensis. Chemical analysis of serum and histopathology of liver and kidney from test animals were performed to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine in serum. In addition, serum albumin levels were also determined. The levels of ALT, AST and creatinine were found to be high in groups treated with crude extracts compared to the control group, suggesting some damage in liver cells and kidney of treated groups of Wistar rats. The albumin levels in serum samples of crude extract treated groups were found to be low compared to control group, suggesting some leakage to the urine due to damage in the kidney. Histopathological analyses revealed damages in the liver and kidney treated with 1000 mg/kg of crude ethanolic pod extracts of Swartzia madagascariensis (CEPES) at days 2 and 14, corresponding to what was observed in the biochemical variables. The findings revealed that Swartzia madagascariensis pods are toxic once taken in large quantities (1000 mg/kg). Keywords: Toxicity, Wistar rats, Histopathology, biochemical parameter

An Integrated Fuzzy Framework for Analyzing Barriers to the Implementation of Continuous Improvement in Manufacturing

Purpose – Delivering premium services and quality products are critical strategies for success in manufacturing. Continuous improvement (CI), as an underlying foundation for quality management, is an ongoing effort allowing manufacturing companies to see beyond the present to create a bright future. We propose a novel integrated fuzzy framework for analyzing the barriers to the implementation of CI in manufacturing companies. Design/methodology/approach – We use the fuzzy failure mode and effect analysis (FMEA) and a fuzzy Shannon’s entropy to identify and weigh the most significant barriers. We then use fuzzy multi-objective optimization based on ratio analysis (MOORA), the fuzzy technique for order of preference by similarity to ideal solution (TOPSIS), and fuzzy simple additive weighting (SAW) methods for prioritizing and ranking the barriers with each method. Finally, we aggregate these results with Copeland’s method and extract the main CI implementation barriers in manufacturing. Findings – We show “low cooperation and integration of the team in CI activities” is the most important barrier in CI implementation. Other important barriers are “limited management support in CI activities,” “low employee involvement in CI activities,” “weak communication system in the organization,” and “lack of knowledge in the organization to implement CI projects.” Originality/value – We initially identify the barriers to the implementation of CI through rigorous literature review and then apply a unique integrated fuzzy approach to identify the most important barriers based on the opinions of industry experts and academics

A retrospective comparison of physical health in regular recreational table tennis participants and sedentary elderly men.

Objectives: This study investigated the benefits of regular recreational table tennis games for body composition, physical performance and muscle strength of older adult men. Methods: We compared twenty older male regular table tennis players (RTTP) and twenty age- and weight-matched sedentary participants (SP). Body composition (LM, lean mass; FM, fat mass; BMD, bone mineral density), physical function, and muscle strength were analyzed with dual-energy X-ray absorptiometry, short physical performance battery (SPPB) and a hand-held dynamometer, respectively. Results: The RTTP had a higher elbow flexor, knee extensor and plantar flexor muscle strength than the SP. The RTTP had a higher total, regional (arm, leg and lumbar spine), and site-specific (trochanter and Ward’s triangle) BMD, and a lower fat mass, in total and regional terms (arm, leg, and truck) as well as percentage of body mass, than the SP. RTTP had a higher SPPB score and performed the 400-m walk in a shorter time than SP. Conclusions: These data suggest that regular table tennis has beneficial effects on muscle strength, physical performance and body composition, and is a potent activity to improve health in older adults

Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection

BACKGROUND: Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-alpha). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-alpha-treatment occur independently of neutropenia. METHODS: We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV). Bacterial titers, numbers of neutrophils and the gene-expression of liver-lysozyme-2 were determined during a 24 hours systemic infection with P. aeruginosa in wild-type and Ifnar(-/-) mice under the influence of LCMV or poly(I:C). RESULTS: Virus-induced IFN-I impaired the control of Pseudomonas aeruginosa. This was associated with neutropenia and loss of lysozyme-2-expression in the liver, which had captured P. aeruginosa. A lower release of IFN-I by poly(I:C)-injection also impaired the bacterial control in the liver and reduced the expression of liver-lysozyme-2. Low concentration of IFN-I after infection with a virulent strain of P. aeruginosa alone impaired the bacterial control and reduced lysozyme-2-expression in the liver as well. CONCLUSION: We found that during systemic infection with P. aeruginosa Kupffer cells quickly controlled the bacteria in cooperation with neutrophils. Upon LCMV-infection this cooperation was disturbed

Intracellular ROS Induction by Ag@ZnO Core–Shell Nanoparticles: Frontiers of Permanent Optically Active Holes in Breast Cancer Theranostic

In this study, we investigated whether ZnO coating on Ag nanoparticles (NPs) tunes electron flux and hole figuration at the metal–semiconductor interface under UV radiation. This effect triggers the photoactivity and generation of reactive oxygen species from Ag@ZnO NPs, which results in enhanced cytotoxic effects and apoptotic cell death in human breast cancer cells (MDA-MB231). In this context, upregulation of apoptotic cascade proteins (i.e., Bax/Bcl2 association, p53, cytochrome c, and caspase-3) along with activation of oxidative stress proteins suggested the occurrence of apoptosis by Ag@ZnO NPs in cancer cells through the mitochondrial pathway. Also, preincubation of breast cancer cells with Ag@ZnO NPs in dark conditions muted NP-related toxic effects and consequent apoptotic fate, highlighting biocompatible properties of unexcited Ag@ZnO NPs. Furthermore, the diagnostic efficacy of Ag@ZnO NPs as computed tomography (CT)/optical nanoprobes was investigated. Results confirmed the efficacy of the photoactivated system in obtaining desirable outcomes from CT/optical imaging, which represents novel theranostic NPs for simultaneous imaging and treatment of cancer

Biphenyl ether analogs containing pomalidomide as small-molecule inhibitors of the programmed cell death-1/programmed cell death-ligand 1 interaction

New biphenyl-based chimeric compounds containing pomalidomide were developed and evaluated for their activity to inhibit and degrade the programmed cell death-1/programmed cell death- ligand 1 (PD-1/PD-L1) complex. Most of the compounds displayed excellent inhibitory activity against PD-1/PD-L1, as assessed by the homogenous time-resolved fluorescence (HTRF) binding assay. Among them, compound 3 is one of the best with an IC50 value of 60 nM. Using an ex vivo PD-1/PD-L1 blockade cell line bioassay that expresses human PD-1 and PD-L1, we show that compounds 4 and 5 significantly restore the repressed immunity in this co-culture model. Western blot data, however, demonstrated that these anti-PD-L1/pomalidomide chimeras could not reduce the protein levels of PD-L1

Direct-to-biology, automated, nano-scale synthesis, and phenotypic screening-enabled E3 ligase modulator discovery

Thalidomide and its analogs are molecular glues (MGs) that lead to targeted ubiquitination and degradation of key cancer proteins via the cereblon (CRBN) E3 ligase. Here, we develop a direct-to-biology (D2B) approach for accelerated discovery of MGs. In this platform, automated, high throughput, and nano scale synthesis of hundreds of pomalidomide-based MGs was combined with rapid phenotypic screening, enabling an unprecedented fast identification of potent CRBN-acting MGs. The small molecules were further validated by degradation profiling and anti-cancer activity. This revealed E14 as a potent MG degrader targeting IKZF1/3, GSPT1 and 2 with profound effects on a panel of cancer cells. In a more generalized view, integration of automated, nanoscale synthesis with phenotypic assays has the potential to accelerate MGs discovery

Integrated Ugi-Based Assembly of Functionally, Skeletally, and Stereochemically Diverse 1,4-Benzodiazepin-2-ones

A practical, integrated and versatile U-4CR-based assembly of 1,4-benzodiazepin-2-ones exhibiting functionally, skeletally, and stereochemically diverse substitution patterns is described. By virtue of its convergence, atom economy, and bond-forming efficiency, the methodology documented herein exemplifies the reconciliation of structural complexity and experimental simplicity in the context of medicinal chemistry projects.This work was financially supported by the Galician Government (Spain), Projects: 09CSA016234PR and GPC-2014-PG037. J.A. thanks FUNDAYACUCHO (Venezuela) for a predoctoral grant and Deputación da Coruña (Spain) for a postdoctoral research grant. A.N.-V. thanks the Spanish government for a Ramón y Cajal research contract

Different formation kinetics and photoisomerization behavior of self-assembled monolayers of thiols and dithiolanes bearing azobenzene moieties

Self-assembled monolayers (SAMs) containing azobenzene moieties are very attractive for a wide range of applications, including molecular electronics and photonics, bio-interface engineering and sensoring. However, very little is known about the aggregation and photoswitching behavior that azobenzene units undergo during the SAM formation process. Here, we demonstrate that the formation of thiol based SAMs containing azobenzenes (denoted as AzoSH) on gold surfaces is characterised by a two step adsorption kinetics, while a three-step assembly process has been identified for dithiolane-based SAMs containing azobenzenes (denoted AzoSS). The H-aggregation on the AzoSS SAMs was found to be remarkably dependent on the time of self-assembly, with less aggregation as a function of time. While photoisomerization of the AzoSH was suppressed for all different assembly times, the reversible trans–cis photoisomerization of AzoSS SAMs formed over 24 hours was clearly observed upon alternating UV and Vis light irradiation. We contend that detailed information on formation kinetics and related optical properties is of crucial importance for elucidating the photoswitching capabilities of azobenzene based SAMs